INVESTIGADORES
MARIÑO Karina Valeria
artículos
Título:
The Tn antigen promotes lung tumor growth by fostering immunosuppression and angiogenesis via interaction with Macrophage Galactose-type lectin 2 (MGL2)
Autor/es:
DA COSTA, VALERIA; VAN VLIET, SANDRA J.; CARASI, PAULA; FRIGERIO, SOFÍA; GARCÍA, PABLO A.; CROCI, DIEGO O.; FESTARI, MARÍA FLORENCIA; COSTA, MONIQUE; LANDEIRA, MERCEDES; RODRÍGUEZ-ZRAQUIA, SANTIAGO A.; CAGNONI, ALEJANDRO J.; CUTINE, ANABELA M.; RABINOVICH, GABRIEL A.; OSINAGA, EDUARDO; MARIÑO, KARINA V.; FREIRE, TERESA
Revista:
CANCER LETTERS
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Lugar: Amsterdam; Año: 2021 vol. 518 p. 72 - 81
ISSN:
0304-3835
Resumen:
Tn is a tumor-associated carbohydrate antigen that constitutes both a diagnostic tool and an immunotherapeutic target. It originates from interruption of the mucin O-glycosylation pathway through defects involving, at least in part, alterations in core-1 synthase activity, which is highly dependent on Cosmc, a folding chaperone. Tn an-tigen is recognized by the Macrophage Galactose-type Lectin (MGL), a C-type lectin receptor present on dendritic cells and macrophages. Specific interactions between Tn and MGL shape anti-tumoral immune responses by regulating several innate and adaptive immune cell programs. In this work, we generated and characterized a variant of the lung cancer murine cell line LL/2 that expresses Tn by mutation of the Cosmc chaperone gene (Tn+LL/2). We confirmed Tn expression by lectin glycophenotyping and specific anti-Tn antibodies, verified abro-gation of T-synthase activity in these cells, and confirmed its recognition by the murine MGL2 receptor. Inter-estingly, Tn+LL/2 cells were more aggressive in vivo, resulting in larger and highly vascularized tumors than those generated from wild type TnLL/2 cells. In addition, Tn+tumors exhibited an increase in CD11c+F4/80+cells with high expression of MGL2, together with an augmented expression of IL-10 in infiltrating CD4+and CD8+T cells. Importantly, this immunosuppressive microenvironment was dependent on the presence of MGL2+cells, since depletion of these cells abrogated tumor growth, vascularization and recruitment of IL-10+T cells. Altogether, our results suggest that expression of Tn in tumor cells and its interaction with MGL2-expressing CD11c+F4/80+cells promote immunosuppression and angiogenesis, thus favoring tumor progression.